Human RNA ligase 1 (Rlig1) is a recently identified human 5’-3’ RNA ligase essential for maintaining 28S rRNA integrity and promoting cell survival under oxidative stress. Although the enzymatic activity of Rlig1 implies a role in RNA maintenance or repair, its broader molecular context remains insufficiently characterised. Here we identify cellular interactors of Rlig1 using affinity enrichment coupled to mass spectrometry in a HEK293 Rlig1-KO model. Our approach revealed several RNA and DNA surveillance, degradation and repair proteins as well as a diverse set of RNA binding and RNA processing enzymes as potential interactors. Notably, ribosomal proteins were highly enriched, suggesting a link between Rlig1 and the translational machinery.